Related Experiment Video

Updated: Dec 5, 2025

Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice
11:10

Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice

Published on: November 16, 2011

95.4K

The deubiquitinase JOSD2 is a positive regulator of glucose metabolism

Lyudmila Krassikova1, Boxi Zhang1, Divya Nagarajan1

  • 1Department of Physiology and Pharmacology, Biomedicum, Karolinska Institutet, Solnavägen 9, SE-171 65, Stockholm, Sweden.

Cell Death and Differentiation
|October 21, 2020
PubMed

Insights

The deubiquitinase JOSD2 promotes cancer cell proliferation by enhancing glucose metabolism. JOSD2 stabilizes key enzymes, impacting tumor growth and offering potential therapeutic targets.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Cancer cells exhibit significant metabolic reprogramming.
  • Understanding the regulation of cancer metabolism is crucial for therapeutic development.

Purpose of the Study:

  • To investigate the role of the deubiquitinase JOSD2 in cancer cell proliferation and metabolism.
  • To elucidate the molecular mechanisms by which JOSD2 influences metabolic pathways.

Main Methods:

  • In vitro and in vivo assays to assess JOSD2's enzymatic activity and cellular effects.
  • Analysis of JOSD2's interaction with metabolic enzyme complexes.
  • Correlation studies between JOSD2 expression and patient prognosis.

Main Results:

  • JOSD2 acts as a positive regulator of cancer cell proliferation.
  • JOSD2 deubiquitinates and stabilizes a metabolic enzyme complex including Aldolase A, Phosphofructokinase-1, and Phosphoglycerate dehydrogenase.
  • JOSD2 enhances glycolytic rate and its deficiency shows cytostatic effects across various tumor types.
  • JOSD2 expression correlates with poor prognosis in non-small cell lung cancer.

Conclusions:

  • JOSD2 integrates glucose and serine metabolism, promoting cancer cell proliferation.
  • JOSD2's specific role in stabilizing metabolic enzymes presents a potential therapeutic vulnerability.
  • Targeting JOSD2 may offer a novel strategy for cancer treatment.

More Related Videos

Visualization of Endogenous Mitophagy Complexes In Situ in Human Pancreatic Beta Cells Utilizing Proximity Ligation Assay08:40

Visualization of Endogenous Mitophagy Complexes In Situ in Human Pancreatic Beta Cells Utilizing Proximity Ligation Assay

Published on: May 2, 2019

6.2K
Glucose Uptake Measurement and Response to Insulin Stimulation in In Vitro Cultured Human Primary Myotubes08:03

Glucose Uptake Measurement and Response to Insulin Stimulation in In Vitro Cultured Human Primary Myotubes

Published on: June 25, 2017

20.5K

Related Concept Videos

Glucose Homeostasis: Regulation of Blood Glucose01:02

Glucose Homeostasis: Regulation of Blood Glucose

Carbohydrates consumed through foods are converted into glucose, a crucial energy source for the body. In the prandial state, high blood glucose levels stimulate the secretion of insulin from the pancreas. Insulin inhibits hepatic glucose production and stimulates glucose uptake and metabolism by muscle and adipose tissue. The excess glucose is converted into glycogen and stored in the liver and muscles.
During fasting, when blood glucose levels are low, the pancreas secretes glucagon. it...
3.4K
Hormones Regulating Blood Glucose01:16

Hormones Regulating Blood Glucose

Insulin is released by beta cells of the pancreas when blood glucose levels are high. It facilitates glucose absorption and utilization in insulin-dependent cells with insulin receptors on their plasma membranes. Insulin promotes glucose uptake by increasing the number of glucose transport proteins in the cell membrane, allowing glucose to enter the cell. As a result, glucose utilization and ATP production are enhanced.
In addition to accelerating glucose uptake and utilization, insulin has...
5.9K
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion01:27

Glucose Homeostasis: Pancreatic Islets and Insulin Secretion

The pancreatic islets comprising only 1%-2% of the volume are highly vascularized and innervated mini-organs. They contain five endocrine cell types, including β cells that secrete insulin, which is synthesized as a single polypeptide chain, preproinsulin, processed to proinsulin, and finally to insulin and C-peptide. This process is complex and regulated, involving the Golgi complex, the endoplasmic reticulum, and the secretory granules of the β cell.
Insulin and C-peptide are...
1.9K
Glucose Absorption Into the Small Intestine01:26

Glucose Absorption Into the Small Intestine

Complex carbohydrates consumed cannot be absorbed into the small intestine in their original form. First, they must be hydrolyzed to a monosaccharide form such as glucose or galactose. These monosaccharides are then transported across the intestinal membrane and into the blood via transcellular transport. The intestinal epithelial cells allow the movement of these monosaccharides with a defined 'entry' through membrane transporter proteins present on their apical membrane and...
34.1K
Regulation of Metabolism01:19

Regulation of Metabolism

Cellular needs and conditions vary from cell to cell and change within individual cells over time. For example, the required enzymes and energetic demands of stomach cells are different from those of fat storage cells, skin cells, blood cells, and nerve cells. Furthermore, a digestive cell works much harder to process and break down nutrients during the time that closely follows a meal compared with many hours after a meal. As these cellular demands and conditions vary, so do the amounts and...
11.0K
Glucose Transporters01:27

Glucose Transporters

Glucose transporters facilitate the transport of glucose across the cell membrane. In addition to glucose, some glucose transporters can also aid the movement of other hexoses such as fructose, mannose, and galactose.
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
26.8K